Immunohistochemistry for c-MET, HLA class II, and CD68 does not show prognostic value in early-stage classic Hodgkin lymphoma patients in the EORTC-GELA H9 intergroup randomised trial.
Rodrigo Martinez Alcala, Lydia Visser, Catherine Fortpied et al.
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In 30 seconds
This case-cohort biomarker validation study examined whether immunohistochemical expression of c-MET, HLA class II, or CD68 predicted progression-free survival in patients with early-stage classic Hodgkin lymphoma enrolled in the EORTC-GELA H9 randomised trial. The analysis included 257 patients and 105 progression-free survival events. None of the three markers was significantly associated with progression-free survival in univariate Cox regression; for example, the hazard ratio was 0.752 for c-MET (95% CI: 0.456-1.241). The investigators therefore did not proceed to analyses combining the biomarkers.
Key findings
- c-MET expression was detected in tumor cells in 67% (108/162) of evaluable cases.
- Cell-surface HLA class II expression was observed in 51% (70/137) of evaluable cases.
- None of the markers was significantly associated with progression-free survival: HRs were 0.752 for c-MET, 0.854 for HLA class II, and 0.864 for CD68.
- No combined-biomarker analyses were performed because none of the individual markers was significantly associated with progression-free survival.
Why it matters
Prognostic tissue markers could help distinguish risk among patients with early-stage classic Hodgkin lymphoma, but these results do not support c-MET, HLA class II, or CD68 as useful predictors of progression-free survival in this trial population. The findings underscore the need for validation before candidate biomarkers are used to inform risk assessment.
What to keep in mind
The analysis was restricted to early-stage patients in one trial; the authors note that risk-adapted treatment, exclusion of advanced-stage disease, and scoring challenges may have affected validation.